WHO Report Highlights Advances in Second-Line HIV Treatment Optimization

A new WHO report sheds light on the latest advancements in optimizing second- and third-line HIV treatment. The comprehensive review calls for updated guidelines that favor safer, more effective regimens like darunavir/ritonavir and recycling tenofovir, emphasizing better management of drug resistance and adherence.

A Closer Look at WHO's New Insights on HIV Treatment Optimization

The recent World Health Organization (WHO) report, titled “Optimization of Second-line and Third-line Antiretroviral Therapy for People Living with HIV,” dives into strategies to enhance the efficacy of HIV treatment worldwide. Held over two days in November 2023, the meeting brought together a coalition of experts, public health leaders, and stakeholders to reassess antiretroviral therapy (ART) and tackle pressing challenges.

Refining Second-Line Therapy with Darunavir/Ritonavir

Central to the discussions was the positioning of darunavir/ritonavir (DRV/r) as a leading protease inhibitor (PI) for patients transitioning to second-line ART. The evidence presented underscored DRV/r's superior efficacy and safety profile compared to alternatives like atazanavir/ritonavir (ATV/r) and lopinavir/ritonavir (LPV/r). However, the report flagged potential barriers such as cost and availability, particularly in low- to middle-income countries. The nuanced analysis suggested that DRV/r's adoption as a primary choice could yield improved patient outcomes but would require strategic financial and logistical planning.

The Case for Recycling Tenofovir

The report also delved into the benefits of recycling tenofovir—both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF)—within second-line treatment regimens. Despite some existing resistance, studies highlighted in the WHO meeting found that reusing TDF or TAF could sustain viral suppression effectively. Notably, TAF showed advantages for bone and renal health, though it came with a caveat: an increased risk of weight gain. The WHO experts emphasized that careful patient assessment and ongoing monitoring are vital for optimizing these regimens.

Addressing Resistance: A Priority

Dolutegravir (DTG), a commonly used integrase strand-transfer inhibitor, was another focal point, with discussions revolving around its resistance risk in certain treatment transitions. While the efficacy of DTG remained a strong anchor for ART, the need to monitor resistance development was clear. The report called for an updated perspective on sequencing treatments and a reconsideration of the current thresholds defining treatment failure.

Evidence and Recommendations

The WHO report backed its findings with data from trials such as NADIA, VISEND, and D2EFT, presenting a mixed landscape where DRV/r and tenofovir recycling emerged as viable pathways for second-line therapy. For children and adolescents, trials like CHAPAS-4 and SMILE supported DRV/r’s effective and safe use.

Future Pathways for ART Guidelines

The culmination of the WHO meeting called for an overhaul of treatment guidelines, advocating for DRV/r as the preferred PI and recommending that tenofovir recycling should be maintained with safety checks. The discussions also highlighted the importance of patient adherence and proactive management, urging a people-centered approach to ART that aligns with varying patient needs across demographics.

The “Optimization of Second-line and Third-line Antiretroviral Therapy for People Living with HIV” report not only showcases the strides made but also shines a spotlight on the work that remains. These insights pave the way for a future where more lives can be sustained through adaptive, evidence-based treatment solutions that prioritize safety, efficacy, and accessibility.

This comprehensive review aligns with the WHO's people-first mission, offering essential, research-backed updates that aim to bolster public health and ensure effective, equitable HIV treatment worldwide.